Project Summary In light of the ongoing chronic pain and opioid epidemic, the Centers for Disease Control have proposed guidelines to primarily employ non-opiate pain therapies. Mindfulness meditation is a potentially cost-effective, self-regulatory practice that reliably reduces acute and chronic pain. However, the specific neural mechanisms engaged by mindfulness meditation to reduce pain have yet to be fully characterized, limiting its clinical utility. Growing evidence suggests that the so-called default mode network (DMN) is involved in facilitating self- referential processes and pain. In particular, a central node of the DMN, the posterior cingulate cortex (PCC), is positively associated with higher pain and aberrant connectivity with brain mechanisms supporting the self- regulation of pain. We postulate that the PCC is an important mechanistic target for behavioral practices like mindfulness meditation that reduce the impact of cognitive and affective appraisals of arising sensory events. To this extent, when compared to active control conditions, mindfulness meditation reliably produces greater PCC deactivation. We recently discovered that higher dispositional mindfulness is associated with lower pain and greater PCC deactivation. However, no known studies have directly examined the role of the PCC in promoting mindfulness-based pain relief. Employing a recently completed blood-oxygen-level-dependent (BOLD) functional neuroimaging study combining noxious heat during mindfulness meditation, the proposed research project will examine if greater PCC deactivation is positively associated with mindfulness-based pain relief (Aim 1). Further, no known studies have identified the neurofunctional connections that are engaged during mindfulness-based pain relief. Our laboratory has repeatedly shown that mindfulness-based analgesia is associated with greater orbitofrontal cortex (OFC) activation, a brain region involved in facilitating unique reappraisal processes. We will conduct functional connectivity analyses to determine if increased connectivity between the PCC and OFC is associated with mindfulness-induced pain relief (Aim 2). The knowledge to be gained from the proposed research activities will provide novel mechanistic insight into the specific analgesic processes associated with mindfulness, an important consideration for the millions of chronic pain patients seeking a non-opioid pain therapy. Importantly, the overarching goal of this F32 training fellowship is to gain the necessary knowledge and skills to reliably conduct brain imaging and corresponding analyses to better prepare me to accomplish my goal to be an independent cognitive neuroscientist. The proposed training activities include a) individualized mentoring from my Sponsor and Co-Sponsors, b) formal training in neuroanatomy, programming, fMRI-based methodologies, and pain-evoking procedures, c) scientifically validated mindfulness training, d) and career development strategies. The proposed research and training activities will ensure I am equipped for an independent research career focused on identifying the mechanisms supporting mindfulness-based pain relief and health promotion.